The goal of this proposal is to obtain a coherent understanding of dynamic hormone, mineral and bone protein responses to brief periods of phosphate administration in human subjects. The importance of this inquiry has been heightened in recent years. For, despite the paucity of data on its effects in human subjects, phosphate has been advocated as a component of therapeutic regimens for osteoporosis. The interactions of phosphate with two indices of bone metabolism - 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and bone GLA protein (BGP) - are of particular interest. There are three specific goals of this project: 1) to compare the effect of brief periods of phosphate administration on indices of mineral metabolism in women with osteoporosis, with the effect in young and older subjects with no bone disease; 2) to investigate the action of phosphate to reduce the circulating levels of 1,25(OH)2D in osteoporosis; 3) to investigate the kinetics of BGP responsiveness to phosphate administration in normal subjects and to determine the hormone or mineral most directly responsible for the rise in BGP after phosphate administration. The project will be carried out in human subjects in order to provide better understanding of the impact of phosphate on the actual subjects in whom we are interested. The process of accomplishing this research will further the candidate's development into an independent clinical investigator. This goal will be guided by Drs. John Bilezikian and Robert Lindsay, the sponsors of this career application, and by the other members of the Division of Hormonal and Metabolic Disorders at the College of Physicians and Surgeons, all of whom are established investigators in the field of bone and mineral metabolism.